Purpose: Postoperative pain is a common and distressing issue following surgical procedures. The neutrophil-tolymphocyte ratio (NLR), which increases during the inflammatory response, is an important indicator influencing the severity of pain. Preemptive analgesia aims to reduce spinal sensitization by administering analgesics before surgery.This study investigates the effect of preoperative intravenous ibuprofen on postoperative pain in patients with high NLRs undergoing laparoscopic cholecystectomy. Methods: The study was conducted as a prospective, randomized, double-blind, placebo-controlled trial. A total of 73 patients aged 18–65 years with American Society of Anesthesiologists physical status I, II were included. Patients were divided into 2 groups based on their NLRs: high (>2) and low (<2). Each group was further divided into subgroups receiving preemptive analgesia (400 mg intravenous ibuprofen) or placebo. Pain levels were measured using the visual analogue scale (VAS), and rescue analgesia requirements were recorded. Results: VAS scores and rescue analgesia needs were significantly lower in patients receiving preemptive ibuprofen compared to the placebo group, regardless of the NLR. However, the inflammatory score did not have a statistically significant effect on postoperative pain or analgesic needs. There were no differences in operative time or discharge duration between groups. Conclusion Preemptive ibuprofen is an effective method for reducing postoperative pain and may decrease opioid consumption. The effects of preemptive analgesia were observed even in patients with high inflammatory scores. Studies with larger sample sizes could improve the generalizability of these findings.